The biological clocks that regulator daily and circadian patterns of daily behavior, physiology and biochemistry are fundamental properties of biological organization. In recent years, great strides have been made in elucidating the anatomical localization of clock structures, the physiology of clock function and the biochemical/molecular events underlying circadian rhythmicity. These advances have been made in diverse organisms, which share many common formal and molecular properties but which differ in the level at which clocks are understood and at which they function. Among the best-studied model systems are the cyanobacterium Synechococcus sp., the filamentous fungus Neurospora crassa, the avail pineal gland and the mammalian suprachiasmatic nucleus (SCN), which have all provided disparate pieces of a very large, complex puzzle. However, a complete picture of this puzzle, of clock input, oscillation and output, is not apparent, because divergent systems provide dissimilar views. This may be due to real biological differences in experimental systems and/or diverse approaches. The present Program Project Grant combines the efforts of 4 established laboratories, which have a history of cooperative education and research, devoted to different aspects of biological clock function in these well-studied model systems. Dr. D.J Earnest (Project #2) will investigate mechanisms of circadian oscillation and its output in a unique immortalized cell line derived from the rat SCN. Dr. D. Bell-Pedersen (Project #3) will explore the relationship of developmental and metabolic processes with circadian rhythm function in Neurospora. Dr. V.M. Cassone (Project #4) will study the molecular mechanisms of rhythm generation and coupling to melatonin biosynthesis in the chick pineal and of cellular mechanisms of melatonin action in cultured glia. Two Technical Cores and an Administrative/Integrative Core will enable will enable each laboratory to extend the boundaries of their own research: 1) The Genomics (Core A), directed by Dr. T. Thomas, will perform modern genomics analyses including high density transcriptional profiling, DNA microarray technology and EST analyses. 2) The Cell Physiology/Imaging Core (Core B), directed by Dr. Mark Zoran, will perform electrophysiological and real-time imaging of gene expression. 3) The Administrative and Integrative Core (Core C), directed by Dr. Cassone, will maintain records, facilitate interaction of laboratories by scheduling of regulate meetings, and coordinate meetings with advisory committees. In addition, this ore will facilitate data analysis of the entire data set collected by all laboratories compiling sequence and functional data, archiving these data and analyzing phylogenetic relationships among these diverse systems. All four projects are bonded by common technological approaches to diverse biological systems and by a commitment to interdisciplinary, comparative analyses of biological clock function.